The most successful drugs for suppressing HIV--protease inhibitors--can strengthen damaged immune systems in the face of resurging HIV. The surprising finding, reported in tomorrow's issue of The Lancet, suggests that all AIDS patients should continue taking protease inhibitors, even if the drugs are not directly suppressing the virus.
The addition of protease inhibitors to the drug "cocktails" AIDS patients take to suppress HIV infections has made a big difference in the effectiveness of the therapies. If treatment begins soon after infection, the drugs can suppress HIV until it is undetectable. The cocktail also boosts the number of CD4 T lymphocytes, immune system cells that attack HIV and other infectious invaders. But in about half of AIDS patients, HIV continues to be detected or reappears months later. Doctors tend to regard this as a sign that the therapy is no longer working and often switch to alternative treatments.
Last year, researchers at Vaudois University Hospital Center in Lausanne, Switzerland, noticed that some AIDS patients who weren't responding to the cocktail, as judged by their having persistent HIV levels, nevertheless seemed to be free of secondary infections. To see if the drugs were helping the immune system rebound, despite the presence of the virus, the researchers continued giving protease inhibitors to 101 outpatients daily. After 48 weeks, the number of CD4 cells in 91 of the patients had on average almost doubled--even among those who still had detectable levels of HIV in their blood. "These people have benefited and are stable," says team member Amalio Telenti. Patients who stopped the protease treatment, on the other hand, dramatically set back their immune system, says Telenti. Their CD4 cell numbers plummeted by as much as two-thirds.
It's not clear why the protease inhibitors help the immune system recover even in the face of continued viral replication. The drugs may somehow render new HIV particles unable to kill the CD4 cells, says David Margolis, a virologist at the Institute of Human Virology in Baltimore. Or the therapy may have some unknown benefit on the immune system itself.